It’ll be an NFC West showdown in Santa Clara on Sunday afternoon as Kyler Murray and the Arizona Cardinals come to town. For the 49ers, it’ll once again be Mac Jones starting the game for the team. Kickoff is scheduled for 4:25 PM ET on Fox. Let’s jump into this Cardinals-49ers preview and predictions.
Arizona comes into this game as one of the three 2-0 NFC West teams. In Week 1, they picked up the win in New Orleans over the Saints. Week 2 brought the Panthers to Arizona, where the Cardinals handled them for 3+ quarters. Carolina made it a game late, but the Cardinals were able to hang on.
San Francisco also comes into this game 2-0 despite a litany of injuries plaguing the team once again. Brock Purdy isn’t ready to return, so it’ll once again be Mac Jones starting at quarterback. Jones looked good starting in place of Purdy last week, but it was against the bad Saints defense. The 49ers’ Week 1 win came against the Seahawks in Seattle.
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Arizona Cardinals at San Francisco 49ers Preview and Predictions
Kyler Murray Over 28.5 Yards (-115)
Kyler Murray loves to run the ball early in the season, and loves to run the ball against the San Francisco 49ers. Last year, late in the season, in Week 18, he had just 22 yards against them on the ground. But in Week 5, he scampered for 83 rushing yards. In four of the first five weeks last season, Kyler easily cleared this mark.
So far in 2025, Murray is two for two going over the 29-yard mark. When he played the 49ers in 2023, he had 49 yards on the ground in his lone game against them. In five of his seven career games against Kyle Shanahan and the 49ers, Kyler has gone over this mark. I’m expecting the Cardinals to have a true shot at winning this game. To do so, they’ll need Kyler to run the ball.
Arizona Cardinals +2.5 (-108)
Arizona is a team I’m high on this year. They’ve played two of the worst teams in the league in the first two weeks, but did what they were supposed to do and got the win. The Cardinals have had the 49ers’ number over their last four meetings, going 3-1 in those four games. Mac Jones is a serviceable backup, but he’s not going to be great every week, and I think the Cardinals get the best of him this week.
